帕洛诺司琼止吐效果怎么样?

In a phase III, multicenter, randomized, double-blind, double-dummy, stratified, parallel-group, active-controlled trial (NCT00359567), we evaluated the efficacy and safety of palosetron versus granisetron for the treatment of chemotherapy-induced nausea and vomiting, both used with dexamethasone in patients receiving highly emetogenic chemotherapy.

1143 cancer patients receiving highly emetic chemotherapy (i.e., cisplatin or anthracycline and cyclophosphamide combination chemotherapy [AC/EC]) were recruited from 75 institutions in Japan and randomized to single-dose palonosetron (0.75 mg) and granisetron (40 microg/kg) 30 minutes before chemotherapy, followed by dexamethasone (16 mg intravenously), followed by additional doses on days 2 and 3 (8 mg intravenously for patients receiving cisplatin or 4 mg orally for patients receiving AC/EC).

Patients were randomized using a non-deterministic minimization method with random biased coins. Covariates known to influence the risk of emesis, such as sex, age, and type of highly emetogenic chemotherapy, were used as minimized stratification factors to ensure balance between treatment groups.

The primary endpoints were the proportion of patients with complete response (defined as the absence of emetic episodes and no rescue medication) in the acute phase (0-24 hours after chemotherapy; non-inferiority comparison with granisetron) and the proportion of patients with complete response in the delayed phase (24-120 hours before chemotherapy; superiority comparison with granisetron).

The noninferiority margin was predefined in the study protocol as a 10% difference in the proportion of patients with complete response between the two groups. The palonosetron dose of 0.75 mg was selected based on two dose-determination trials in Japanese patients. All patients who received study treatment and highly emetogenic chemotherapy were included in the efficacy analysis (modified intention-to-treat).

Results: 1,114 patients were included in the efficacy analysis: 555 patients in the granisetron group and 559 patients in the granisetron group. 418 of 555 patients (75.3%) in the palonosetron group had a complete response in the acute phase compared with 410 of 559 patients (73.3%) in the granisetron group (mean difference 2.9%), and 315 of 555 patients (56.8%) in the palonosetron group had a complete response compared with 249 of 559 patients (44.5%) in the granisetron group.

Treatment-related conditions were mainly constipation (97 of 557 patients (17.4%) in the palonosetron group vs. 88 of 562 (15.7%) in the granisetron group) and increased serum aminotransferase concentrations (aspartate aminotransferase: 24 of 557 [4.3%] vs. 34 of 562 [6.0%]; alanine aminotransferase: 16 of 557 [2.9%] vs 33 of 561 [5.9%]); no grade 4 major treatment-related adverse events were reported.

Conclusions: When dexamethasone is given before highly emetogenic chemotherapy, palonosetron is no less effective than granisetron in the acute phase and superior to granisetron in the delayed phase in treating chemotherapy-induced nausea and vomiting. The safety profiles of the two treatments were comparable.

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References

Saito M, Aogi K, Sekine I, Yoshizawa H, Yanagita Y, Sakai H, Inoue K, Kitagawa C, Ogura T, Mitsuhashi S. Palonosetron plus dexamethasone versus granisetron plus dexamethasone for prevention of nausea and vomiting during chemotherapy: a double-blind, double-dummy, randomized, comparative phase III trial. Lancet Oncol. 2009 Feb;10(2):115-24. doi: 10.1016/S1470-2045(08)70313-9. Epub 2009 Jan 8. Erratum in: Lancet Oncol. 2010 Mar;11(3)226. PMID: 19135415.